Prognostic importance of Aurora Kinases and mitotic spindle genes transcript levels in Myelodysplastic syndrome

Leuk Res. 2018 Jan:64:61-70. doi: 10.1016/j.leukres.2017.11.013. Epub 2017 Nov 28.

Abstract

Myelodysplastic syndrome (MDS) are a heterogeneous group of clonal disease characterized by insufficiency of bone marrow, increase of apoptosis and increased risk of acute leukemia progression. Proteins related to the mitotic spindle (AURKA, AURKB, TPX2), to the mitotic checkpoint (MAD2, CDC20) and the regulation of the cell cycle (p21) are directly related to chromosomal stability and tumor development. This study aimed to evaluate the mRNA expression levels of these genes in 101 MDS patients using a real-time PCR methodology. We identified that CDC20 expression are increased in patients with dysmegakaryopoiesis (p=0.024), thrombocytopenia (p=0.000) and high-risk patients (p=0.014, 0.018) MAD2 expression are decreased in patients with 2 or 3 cytopenias (p=0.000) and neutrophil below 800/mm3. TPX2 is also overexpressed in patients presenting dysmegakaryopoiesis (p=0.009). A decrease in AURKA and AURKB expression were observed in patients with altered karyotype (p=0.000), who presented dysplasia in 3 lineages (p=0.000; 0.017) and hemoglobin inferior to 8g/dL (p=0.024). The expression of AURKA, AURKB and MAD2 (p=0.000; 0.001; 0.025) were decreased in patients with hypoplastic MDS, associated with high frequency of chromosomal alterations and high mortality rate. This study reaffirms the importance of aurora kinases and mitotic spindle genes to the pathogenesis and clinical evolution of MDS.

Keywords: Cancer biology; Cell cycle; Mitotic checkpoint; Mitotic spindle; Myelodysplastic syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aurora Kinase A / genetics
  • Aurora Kinase A / metabolism
  • Aurora Kinase B / genetics
  • Aurora Kinase B / metabolism
  • Cdc20 Proteins / genetics
  • Cdc20 Proteins / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Mad2 Proteins / genetics
  • Mad2 Proteins / metabolism
  • Male
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Middle Aged
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / mortality
  • Myelodysplastic Syndromes / pathology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Prognosis
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism
  • Transcriptome
  • Young Adult
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism

Substances

  • Cdc20 Proteins
  • Cell Cycle Proteins
  • MAD2L1 protein, human
  • Mad2 Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • TPX2 protein, human
  • CDC20 protein, human
  • AURKA protein, human
  • AURKB protein, human
  • Aurora Kinase A
  • Aurora Kinase B
  • rho GTP-Binding Proteins